Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein. Oncotarget 2015 Apr 10;6(10):7815-27
Date
03/23/2015Pubmed ID
25796556Pubmed Central ID
PMC4480718DOI
10.18632/oncotarget.3485Scopus ID
2-s2.0-84928393842 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Our previous studies have demonstrated that expression of epidermal fatty acid binding protein (E-FABP) in tumor associated macrophages (TAMs) promotes macrophage anti-tumor activity by enhancing IFNβ responses in tumor models. Thus, E-FABP represents a new protective factor in enhancing tumor immune surveillance against tumor development. Herein, we report the compound 5-(benzylamino)-2-(3-methylphenyl)-1,3-oxazole-4-carbonitrile (designated EI-05) as a novel E-FABP activator for inhibition of mammary tumor growth. EI-05 was selected from the ZINC compound library using molecular docking analysis based on the crystal structure of E-FABP. Although EI-05 is unable to bind E-FABP directly, it significantly increases E-FABP expression in macrophages during inflammation. Stimulation of macrophages with EI-05 remarkably enhances lipid droplet formation and IFNβ production, which further promotes the anti-tumor activity of macrophages. Importantly, administering EI-05 in vivo significantly inhibits mammary tumor growth in a syngeneic mouse model. Altogether, these results suggest that EI-05 may represent a promising drug candidate for anti-tumor treatment through enhancing E-FABP activity and IFNβ responses in macrophages.
Author List
Rao E, Singh P, Zhai X, Li Y, Zhu G, Zhang Y, Hao J, Chi YI, Brown RE, Cleary MP, Li BAuthor
Young-In Chi PhD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsFatty Acid-Binding Proteins
Female
Humans
Interferon-beta
Macrophage Activation
Macrophages
Mammary Neoplasms, Experimental
Mice
Models, Molecular
Nitriles
Oxazoles
